Under the terms of our agreement, Vernalis will receive a share of sub-licensing income, a milestone payment on approval of RPL554, and will be due royalties on commercialisation.

Proof of concept in asthma and allergic rhinitis

Partnered with Verona Pharma

Royalties and other payments due to Vernalis

Background

PDE 3 and PDE 4 are two enzymes implicated in the development and progression of immunological respiratory diseases, particularly rhinitis (hay fever) and asthma. RPL554 is a long-acting inhibitor of both these enzymes, and this action makes it a potential treatment for respiratory disease. As a PDE 3 inhibitor, the drug is expected to result in bronchodilator actions, whilst the PDE 4 component is expected to be anti-inflammatory.

Verona has successfully completed two double-blind placebo-controlled randomised Phase II studies of RPL554: one in mild to moderate asthma and another in mild to moderate COPD. Verona has reported that the drug was found to be well tolerated, free from drug-related adverse effects (especially cardiovascular and gastrointestinal effects) and generated significant bronchodilation. Additionally, double-blind placebo-controlled exploratory studies in healthy volunteers challenged with an inhaled irritant also generated consistent, clinically meaningful anti-inflammatory effects.

In addition, further clinical studies will be undertaken to continue to prepare RPL554 for larger Phase IIb studies in hospitalised COPD patients using a nebulised formulation. It is expected that key data from these activities will be reported in 2015 and 2016.

Vernalis will receive a share of sub‑licensing income, a milestone payment on approval of RPL554 and royalties on commercialisation.

Pre-clinical studies

RPL554 has successfully completed a number of pre-clinical studies.

Clinical studies

In September 2012, data from a Phase II study was presented by Professor Mario Cazzola, Principal Investigator, at the European Respiratory Society (ERS) Annual Congress in Vienna.

The Phase II trial was a placebo-controlled cross-over study in 12 patients with mild to moderate COPD. The data showed that a single dose of nebulized RPL554 to patients with COPD produced a rapid bronchodilator response, greater than a 15% increase in FEV1 (forced expiratory volume at 1 second). This was significantly larger than that produced by placebo and appeared to be at least equivalent to that produced by a standard dose of the reference bronchodilator beta2-agonist salbutamol in these patients.

A further Phase II trial in mild to moderate asthma has also been completed and further double-blind placebo-controlled exploratory studies in healthy volunteers challenged with an inhaled irritant also generated consistent, clincially meaningful anti-inflammatory effects. In addition, RPL554 was well tolerated and did not cause any significant adverse effects.

Further clinical studies will be undertaken to continue to prepare RPL554 for larger Phase IIb studies in hospitalised COPD patients. Key data from these activities is expected to be reported in 2016.

Project Status

Phase I and II clinical studies completed, ready for key data from further Phase II studies. Further clinical studies will be undertaken to continue to prepare RPL554 for larger Phase IIb studies in hospitalised COPD patients. Key data from these activities is expected to be reported in 2016. Verona Pharma successfully completed a £14 million fund raising in March 2014, the proceeds of this are to be used to further develop RPL554.